Browsing by Author "Pellman, David"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Centrosomes and cilia in human diseasePublication . Bettencourt-Dias, Mónica; Hildebrandt, Friedhelm; Pellman, David; Woods, Geoff; Godinho, Susana A.Centrioles are microtubule-derived structures that are essential for the formation of centrosomes, cilia and flagella. The centrosome is the major microtubule organiser in animal cells, participating in a variety of processes, from cell polarisation to cell division, whereas cilia and flagella contribute to several mechanisms in eukaryotic cells, from motility to sensing. Although it was suggested more than a century ago that these microtubule-derived structures are involved in human disease, the molecular bases of this association have only recently been discovered. Surprisingly, there is very little overlap between the genes affected in the different diseases, suggesting that there are tissue-specific requirements for these microtubule-derived structures. Knowledge of these requirements and disease mechanisms has opened new avenues for therapeutical strategies. Here, we give an overview of recent developments in this field, focusing on cancer, diseases of brain development and ciliopathies.
- Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregationPublication . Marteil, Gaëlle; Guerrero, Adan; Vieira, André F; de Almeida, Bernardo P; Machado, Pedro; Mendonça, Susana; Mesquita, Marta; Villarreal, Beth; Fonseca, Irina; Francia, Maria E; Dores, Katharina; Martins, Nuno P; Jana, Swadhin C; Tranfield, Erin M; Barbosa-Morais, Nuno L; Paredes, Joana; Pellman, David; Godinho, Susana A; Bettencourt-Dias, MónicaCentrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.